Characterization of Effectiveness in Concerted I h Inhibition and I K(Ca) Stimulation by Pterostilbene (Trans-3,5-dimethoxy-4′-hydroxystilbene), a Stilbenoid

摘要

Pterostilbene (PTER), a natural dimethylated analog of resveratrol, has been demonstrated to produce anti-neoplastic or neuroprotective actions. However, how and whether this compound can entail any perturbations on ionic currents in electrically excitable cells remains unknown. In whole-cell current recordings, addition of PTER decreased the amplitude of macroscopic I h during long-lasting hyperpolarization in GH 3 cells in a concentration-dependent manner, with an effective IC 50 value of 0.84 μM. Its presence also shifted the activation curve of I h along the voltage axis to a more hyperpolarized potential, by 11 mV. PTER at a concentration greater than 10 μM could also suppress l -type Ca 2+ and transient outward K + currents in GH 3 cells. With the addition of PTER, I K(Ca) amplitude was increased, with an EC 50 value of 2.23 μM. This increase in I K(Ca) amplitude was attenuated by further addition of verruculogen, but not by tolbutamide or TRAM-39. Neither atropine nor nicotine, in the continued presence of PTER, modified the PTER-stimulated I K(Ca) . PTER (10 μM) slightly suppressed the amplitude of l -type Ca 2+ current and transient outward K + current. The presence of PTER (3 μM) was also effective at increasing the open-state probability of large-conductance Ca 2+ -activated K + (BK Ca ) channels identified in hippocampal mHippoE-14 neurons; however, its inability to alter single-channel conductance was detected. Our study highlights evidence to show that PTER has the propensity to perturb ionic currents (e.g., I h and I K(Ca) ), thereby influencing the functional activities of neurons, and neuroendocrine or endocrine cells.